Flaviviridae RdRp利用NSUN2驱动的m5C甲基化来建立持久性感染
Jing Chen1,2, Lin Han Zhong1,2, Jin Xia Chen1,2
1MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
PLoS pathogens
|December 4, 2025
概括
日本脑炎病毒 (JEV) 通过稳定NSUN2,RNA修饰的关键酶,劫持宿主表观转录机械. 这一过程减弱了抗病毒免疫力,促进了病毒的持久性,并提出了新的治疗点.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 由于免疫逃避和持续的感染,Flaviviridae病毒导致了重大的全球健康问题.
- 缺乏广泛的抗病毒疗法.
- 在宿主-病原体相互作用中,RNA的修饰,特别是5-甲基细胞素 (m5C),至关重要.
研究的目的:
- 调查表皮转录机械在日本脑炎病毒 (JEV) 感染中的作用.
- 阐明JEV逃避宿主免疫反应的机制.
主要方法:
- 研究了JEV编码的RNA依赖RNA聚合酶 (RdRp) 与宿主因子之间的相互作用.
- 评估了NSUN2稳定对Cebpd mRNA和cGAS-STING信号传导的影响.
- 在其他病毒家族中检查了同源机制.
主要成果:
- JEV RdRp通过SAE1.1诱导NSUN2的SUMO3/4介导稳定.
- 升高的NSUN2增强了CebpdmRNA的m5C甲基化,导致其降解.
- 这一过程抑制了cGAS-STING抗病毒信号,促进了病毒复制.
- 在Orthomyxoviridae感染中观察到类似的机制.
结论:
- 一个保存的RdRp-SAE1-NSUN2-CEBPD轴代表了一个关键的表皮转录性免疫逃避策略.
- m5C甲基转移酶是广泛抗病毒疗法的潜在标.
相关概念视频
Retrovirus Life Cycles
49.2K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
49.2K
Viruses with RNA Genomes
751
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
751
Retroviruses
14.6K
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
14.6K
Size and Structure of Viral Genomes
626
Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
626
Viral Mutations
39.6K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
39.6K
Mechanisms of Retrovirus-induced Cancers
6.8K
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
6.8K


